The development of new technology for the newborn screening of Hunter syndrome (mucopolysaccharidosis-II) is warranted because of the development of treatments which are most effective when started early in life. This lysosomal storage disease is caused by deficiency in the enzyme iduronate-2-sulfatase, which is needed for the degradation of dermatan sulfate and heparan sulfate, two components of cellular glycosaminoglycans. The assay of this sulfatase requires the use of α-L-iduronate glycosides containing a sulfate at the 2-position.
Synthetic substrates used to assay iduronate-2-sulfatase in vitro are usually disulfated disaccharides derived from nitrous acid degradation of heparin. Such substrates have been useful for the development of a tandem mass spectrometry assay for the newborn screening of Hunter syndrome. However, more recently it has become apparent that the scale-up synthesis using nitrous acid degradation of heparin is impractical to obtain the amount of material needed to support worldwide newborn screening of Hunter syndrome.
A need exists for a new method for the total synthesis of appropriate substrates that can be used at the tens of grams per year scale.